1. Field of the Invention
The present invention relates to a method of treating an ocular condition, comprising the step of placing a biodegradable intraocular implant in an eye of the patient, the implant comprising a prostamide and a biodegradable polymer matrix that releases drug at a rate effective to sustain release of an amount of the prostamide from the implant to provide an amount of the prostamide effective to prevent or reduce a symptom of the ocular condition, wherein said ocular condition is elevated IOP.
2. Summary of the Related Art
The anterior and posterior chambers of the eye are filled with aqueous humor, a fluid predominantly secreted by the ciliary body with an ionic composition similar to the blood. The function of the aqueous humor is two-fold: to 1) supply nutrients to the avascular structures of the eye, such as the lens and cornea and 2) maintain intraocular pressure (IOP) within its physiological range. Maintenance of IOP and supply of nutrients to the anterior segment are factors that are critical for maintaining normal visual acuity. Aqueous humor is predominantly secreted to the posterior chamber of the eye by the ciliary processes of the ciliary body and a minor mechanism of aqueous humor production is through ultrafiltration from arterial blood. Aqueous humor then reaches the anterior chamber by crossing the pupil and there are convection currents where the aqueous, adjacent to the iris, flows upwards, and the aqueous, adjacent to the cornea, flows downwards. There are two different pathways of aqueous humor outflow, both located in the iridocorneal angle of the eye. The uveoscleral or nonconventional pathway refers to the aqueous humor leaving the anterior chamber by diffusion through intercellular spaces among ciliary muscle fibers. Although this seems to be a minority outflow pathway in humans, the uveoscleral or nonconventional pathway is the target of specific anti-hypertensive drugs such as the hypotensive lipids, e.g. bimatoprost, that increase the functionality of this route through remodeling of the extracellular matrix. In addition, bimatoprost may improve aqueous outflow through the trabecular meshwork (“TM”) mediated through a prostamide receptor. In the human eye, the main outflow route is the trabecular or conventional outflow pathway. This tissue contains three differentiated layers. From the inner to the outermost part, the layer of tissue closest to the anterior chamber is the uveal meshwork, formed by prolongations of connective tissue arising from the iris and ciliary body stromas and covered by endothelial cells. This layer does not offer much resistance to aqueous humor outflow because intercellular spaces are large. The next layer, known as the corneoscleral meshwork, is characterized by the presence of lamellae covered by endothelium-like cells on a basal membrane. The lamellae are formed by glycoproteins, collagen, hyaluronic acid, and elastic fibers. The higher organization of the corneoscleral meshwork in relation to the uveal meshwork as well as their narrower intercellular spaces are responsible for the increase in flow resistance. The third layer, which is in direct contact with the inner wall of endothelial cells from Schlemm's canal, is the juxtacanalicular meshwork. It is formed by cells embedded in a dense extracellular matrix, and the majority of the tissue resistance to aqueous flow is postulated to be in this layer, due to its narrow intercellular spaces. The layer of endothelial cells from Schlemm's canal has expandable pores that transfer the aqueous into the canal and accounts for approximately 10% of the total resistance. It has been postulated that aqueous humor crosses the inner wall endothelium of Schlemm's canal by two different mechanisms: a paracellular route through the junctions formed between the endothelial cells and a transcellular pathway through intracellular expandable pores of the same cells. Once there is entry into Schlemm's canal, the aqueous drains directly into the collector ducts and aqueous veins that anastomose with the episcleral and conjunctival plexi of vessels. Aqueous humor outflow via the trabecular pathway is IOP dependent, usually measured as outflow facility, and expressed in microliters per minute per millimeter of mercury. The episcleral venous pressure controls outflow through the collector channels and is one factor that contributes to the intraocular pressure. Increases in the episcleral venous pressure such as seen with carotid-cavernous sinus fistulas, orbital varices, and Sturge-Weber Syndrome, can lead to difficult to manage glaucoma. Reducing episcleral venous pressure in disease states, such as treating carotid-cavernous sinus fistulas, can normalize the episcleral venous pressure and reduce the intraocular pressure. The mechanism of action of modern ocular hypotensive agents for treating ocular hypertension and open angle glaucoma are as follows: 1—reduce aqueous humor production, 2—improve uveoscleral outflow, 3—improve outflow through the TM with miotic agents by providing tension as the scleral spur with stimulation of the ciliary body muscle, 4—combination of any of the above.